We propose to develop synthetic methodology which would be useful in syntheses of chemotherapeutics and to investigate model reactions of important biological processes. In both areas the processes to be studied are based on previous discoveries of new and/or novel chemistry in our laboratories. The use of alpha-heteroatom dipole stabilized carbanions in a synthetic sequence which provides electrophilic substitution adjacent to the heteroatoms of primary alcohols and all thiols via the metalated esters and thioesters is proposed to be extended to secondary alcohols and amines by the preparation of esters and amides specifically designed for facile hydrolysis after electrophilic substitution. The role of dipole stabilized carbanions in enzymatic decarboxylations will be evaluated in model studies. Extension of the use of secondary and tertiary amides, which we have shown to be the most powerful activities for ortho methalation, in regiospecific syntheses substituted of heteromatic and alicyclic systems is to be studied. The use of heterophilic additions to give synthetic equivalent of electrophilic oxygen and nitrogen at the oxidation level of alcohols and amines will be investigated. Model studies of methylations of protomeric systems and olefins will be carried out.